Design, Synthesis and Biochemical Evaluation of Novel Ethanoanthracenes and Related Compounds to Target Burkitt's Lymphoma

Pharmaceuticals
Andrew J ByrneMary J Meegan

Abstract

Lymphomas (cancers of the lymphatic system) account for 12% of malignant diseases worldwide. Burkitt's lymphoma (BL) is a rare form of non-Hodgkin's lymphoma in which the cancer starts in the immune B-cells. We report the synthesis and preliminary studies on the antiproliferative activity of a library of 9,10-dihydro-9,10-ethanoanthracene based compounds structurally related to the antidepressant drug maprotiline against BL cell lines MUTU-1 and DG-75. Structural modifications were achieved by Diels-Alder reaction of the core 9-(2-nitrovinyl)anthracene with number of dienophiles including maleic anhydride, maleimides, acrylonitrile and benzyne. The antiproliferative activity of these compounds was evaluated in BL cell lines EBV- MUTU-1 and EBV+ DG-75 (chemoresistant). The most potent compounds 13j, 15, 16a, 16b, 16c, 16d and 19a displayed IC50 values in the range 0.17-0.38 μM against the BL cell line EBV- MUTU-1 and IC50 values in the range 0.45-0.78 μM against the chemoresistant BL cell line EBV+ DG-75. Compounds 15, 16b and 16c demonstrated potent ROS dependent apoptotic effects on the BL cell lines which were superior to the control drug taxol and showed minimal cytotoxicity to peripheral blood mononuclear cells (PBMCs). The...Continue Reading

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Citations

Dec 31, 2020·Bioorganic Chemistry·Zefeng ZhaoXiaohui Zheng
Aug 21, 2021·The Journal of Organic Chemistry·Tanawat PhumjanPoonsakdi Ploypradith

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Methods Mentioned

BETA
NMR
X-ray
column chromatography
biopsy
Assay
Fluorescence

Software Mentioned

Bruker APEX
EADP
MMFF94s
PLATON
EXYZ
MOE ( Molecular Operating Environment )
Olex2
SQUEEZE

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